Cancer drug gets escort from new polymer being developed by UB engineers

BUFFALO, NY – You may not have heard of polyethylene glycol (PEG), but chances are you’ve ingested it.

Non-toxic polymers are commonly used to prevent freezer burn in ice cream, moisten toothpaste and, more importantly, help cancer drugs reach their targets and stay longer in the body. .

Excessive amounts of PEG in foods, cosmetics, and pharmaceuticals can produce antibodies against PEG. In some cases, this can even cause allergic reactions or make PEG-coated drugs less effective.

That’s why researchers at the University of Buffalo are investigating alternative polymers for carrying cancer drugs into the body, known as zwitterionic polymers.

“The main advantage of zwitterionic polymers is the immune response. Unlike PEG, there are currently no antibodies against zwitterionic polymers,” said Dr. Chong Cheng, professor in the UB Department of Chemistry and Biotechnology within the School of Engineering and Applied Sciences (SEAS). said.

Cheng is a Principal Investigator with a $2.4 million grant from the National Institute of Biomedical Imaging and Biotechnology, one of the National Institutes of Health.

Co-investigators are Associate Professor Yun Wu, Ph.D., and Eugene Y.-X. Chen, Ph.D., of the UB Biomedical Engineering Department, a joint program of SEAS and the Jacobs School of Medicine and Biomedical Sciences, and Professor of Chemistry, Colorado State University.

During the four-year grant cycle starting April 1, the team will be testing a zwitterionic polymer-drug conjugate (ZPDC) to treat pancreatic cancer, considered the deadliest type of cancer in the human body. We investigate whether it can function as a new drug delivery system.

“Our new ZPDC addresses significant challenges facing current drug delivery systems, such as PEG immunogenicity and co-delivery of drugs with incompatible properties,” said Wu. “Thus, we can provide cancer patients with more effective treatments and ultimately improve patient outcomes.”

Limitations of PEG-based drugs

Many targeted cancer therapies come in the form of small molecule drugs that can easily enter cells due to their small molecular weight.

“But small molecules are so small that they are quickly filtered by the kidneys,” says Cheng. “Therefore, the therapeutic window for treating this disease is very narrow.”

Because PEG is composed of large, water-soluble molecules, pharmaceutical companies attach PEG to certain drugs, such as cancer drugs, in a process called PEGylation. This prevents the drug from being broken down before it reaches its target and prolongs its circulation in the bloodstream.

PEG’s ability as a humectant and stabilizer has also made it a popular additive in processed foods and cosmetics.

Although the U.S. Food and Drug Administration classifies PEG as “generally recognized as safe,” a 2016 study in the journal Analytical Chemistry found that as many as 72% of people have detectable levels of anti-PEG antibodies. increase. Studies have found that only a small percentage have enough antibodies to risk an allergic reaction, but those who do can suffer from rashes, hives, and trouble breathing.

Both Moderna and Pfizer Biotech’s mRNA COVID-19 vaccines use PEG to stabilize lipid nanoparticles. Recommended.

In addition to causing allergic reactions, PEG antibodies can interfere with the action of PEGylated drugs.

“PEG antibodies push the PEG agent out of biological systems, which severely limits the efficiency of the delivery system,” says Cheng. “This is the main limitation of PEG-based therapies.”

Substitute with ZPDC

There are currently no ZPDCs on the market. Building on a successful proof-of-concept demonstration, the UB-led team will investigate his ZPDCs through physicochemical, cellular, and in vivo studies.

Besides the lack of immune response, ZPDC has other advantages as well. Cheng says there is a high level of hydration that allows the drug to stay in the body longer than PEGylated drugs.

“So our therapeutic window may be even wider,” he says.

And while most ZPDCs currently being studied are non-biodegradable, Cheng’s team said they designed ZPDC to be biodegradable.

“This is very relevant for biomedical applications, because otherwise accumulation of ZPDCs in biological systems would lead to side effects,” he says.

Cheng says PEG is still a good approach for most patients, but its continued widespread use makes it all the more important to find viable alternatives.

“This is a good opportunity to go in an interesting direction and potentially benefit a lot of people,” says Cheng. “In this way, we increase therapeutic efficacy and improve health and quality of life.”